N-[2-acetamido-3-O-(D-ethyl-1-carbonyl)-2-deoxy-D-glucose]-L-alanyl-D-isogl utamine (muramyldipeptide or MDP) was proposed in 1974-1975 (Ellouz, et al., Biochem, Biophys. Res. Comm., 59, 317 (1974) and Merser, et al., Biochem. Biophys. Res. Comm., 66, 1316 (1975) to be the minimal structure required to express the full spectrum of adjuvant activity when substituted for mycobacteria in Freund's complete adjuvant. Since that time, considerable synthetic efforts, coupled with bioassays have resulted in chemical modifications of MDP with improved immunoadjuvant properties and reduced toxicity.
For example, U.S. Pat. No. 4,082,736, issued Apr. 4, 1978 to Jones, Moffatt and Nestor, describes a family of compounds which are useful as immunological adjuvants. One of the compounds encompassed within the scope of that patent is N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine. This compound is particularly useful as an adjuvant for vaccines, but previously was known only in its amorphous form. In this form, the compound suffered disadvantages of being hygroscopic and chemically reactive at high temperatures. These disadvantages presented certain handling, storage and formulation problems.
It has now been found that the compound N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine (ABU-MDP) can be prepared as a crystalline monohydrate. This novel crystalline monohydrate is substantially more stable under heat and humidity than is amorphous ABU-MDP and thus overcomes the previous disadvantages of the amorphous ABU-MDP. The new crystalline monohydrate is useful as an adjuvant for vaccines and as an immunostimulant.